Urinary incontinence is a condition in which involuntary leakage of urine is involved and recognized objectively and these become social or hygienic problems (Journal of Clinical Pharmacy and Therapeutics, 25, 251-263 (2000)). As typical examples of urinary incontinence, stress urinary incontinence, urge urinary incontinence, functional urinary incontinence, reflex urinary incontinence, overflow urinary incontinence, a mixed type of urinary incontinence which involves stress urinary incontinence and urge urinary, and the like have been known.
The most common type of the urinary incontinence is stress urinary incontinence and it has been reported that 50% of women suffering from the urinary incontinence is stress urinary incontinence (International Urogynecology Journal, 11 (5), 301-319 (2000)). The stress urinary incontinence refers to a disease in which when abdominal pressure rises during coughing, sneezing, exercise, or the like, urine leaks out involuntarily even though there is no contraction of the bladder. The causes of stress urinary incontinence can be largely divided into two types. One is the bladder neck/urethra hypermobility, in which the transmission of abdominal pressure to the urethra fails due to bladder neck ptosis, based on the pelvic floor muscle relaxation, and thus only the intravesical pressure rises during the rise of abdominal pressure and urine leaks. The other is that the reduction of a sphincter muscle function due to intrinsic sphincter deficiency causes urine leakage when the abdominal pressure rises. There is a high possibility that the onset of stress urinary incontinence involves weakening of the pelvic floor muscles due to aging and childbirth, and deterioration of the urethral function. In particular, the trauma of the pelvis by pregnancy and vaginal childbirth is known as a risk factor for a persistent stress urinary incontinence onset, and it has been reported that a prevalence rate of stress urinary incontinence for five years after the first birth is about 30% (Neurourology and Urodynamics, 21 (1), 2-29 (2002)).
Urge urinary incontinence is a disease in which urine leaks involuntarily immediately after a complaint of a strong suddenly occurring and irrepressible desire to urinate which is hard to endure (urge and sudden desire of urination). The mixed type of urinary incontinence is a condition in which a combination of plural types of urinary incontinence is developed, and most of them involve development of urge urinary incontinence and stress urinary incontinence.
Urinary incontinence has a major impact on the quality of life (QOL). Concerns about its symptoms restrict the range of activities of patients, making the patients feel loneliness and social isolation.
As a therapeutic drug for stress urinary incontinence, duloxetine having a serotonin-norepinephrine reuptake inhibitory action (SNRI) has been reported (International Urogynecology Journal, 14, 367-372 (2003)).
Duloxetine has been reported to be effective against stress urinary incontinence in clinical trials, but has also been reported to have side effects such as nausea, insomnia, and dizziness (BJU International, 94, 31-37 (2004)).
In the neuroreflex of the autonomic nerves by stretch stimulus of the bladder in the urine storage phase, an α1 adrenoceptor is present in the urethra and plays a role to maintain continence by inducing urethral contraction. To date, it has been reported that a plurality of drugs having α1 adrenoceptor agonistic actions have a strong urethral contraction action, and in clinical trials, a drug having an α1 adrenoceptor agonistic action is effective against stress urinary incontinence (Journal of Clinical Pharmacy and Therapeutics, 25, 251-263 (2000), International Urogynecology Journal, 14, 367-372 (2003), Urology, 62 (Sup 4 A), 31-38 (2003), and BJU International, 93, 162-170 (2004)). However, it has been known that an α1 adrenoceptor agonist has cardiovascular side effects such as increased blood pressure or the like (International Urogynecology Journal, 14, 367-372 (2003) and BJU International, 93, 162-170 (2004)).
As described above, it is considered that as a drug treatment for stress urinary incontinence, it is effective to increase the urethral resistance so as to maintain continence when intravesical pressure rises during the urine storage phase, and thus, drugs based on some mechanisms of action have been studied. However, there is a strong desire for the development of an agent for treating stress urinary incontinence, based on a novel mechanism of action with fewer side effects.
Meanwhile, melatonin represented by the following formula is a hormone secreted by the pineal gland, which exhibits an inhibitory effect on the function and growth of gonad. Melatonin affects the circadian rhythm in animals, and plays a role to tune the reproductive function to a light cycle of the environment.

As the receptors of melatonin, there have been known three subtypes, MT1, MT2, and MT3 (Cell and Tissue Research, 309, 151-162 (2002) and Journal of Biological Chemistry 275, 31311-31317 (2000)). MT1 and MT2 are G protein-coupled receptors (GPCR) which are coupled to Gi and Gq, but MT3 is a quinone reductase (QR2) which has a melatonin binding site. The affinity of melatonin for the MT1 and MT2 receptors is high, but the affinity of melatonin for the MT3 receptor is low (Journal of Biological Chemistry 275, 31311-31317 (2000)).
Incidentally, there have been a number of reports that MT1 and/or MT2 receptor agonists are useful for the treatment of central nervous system diseases such as sleeping disorders and depression.
As the representative MT1 and/or MT2 receptor agonists, the following compounds have been reported.
A compound represented by the following formula (A) has an MT1 and MT2 receptor agonistic activity and can be used for preventing or treating sleep-awake rhythm disorders, jet lag, abnormality of physical conditions due to work in three shifts or the like, seasonal depression disorder, reproductive and neuroendocrine diseases, senile dementia, Alzheimer's disease, various disorders due to aging, cerebral circulatory disorder, head injury, spinal cord injury, stress, epilepsy, convulsions, anxiety, depression, Parkinson's disease, hypertension, glaucoma, cancer, insomnia, diabetes mellitus, and the like. The compound has been reported to have properties of modulating immunomodulation, intelligence, tranquilizers, and ovulation control (Patent Document 1). In particular, ramelteon represented by the following formula has been known as an agent for treating insomnia characterized by hypnagogic disorder (Non-Patent Documents 1 and 2).

(Refer to this publication for the symbols in the formula.)
It has been described that a compound represented by the formula (B) has an affinity for a melatonin receptor and is useful for the treatment of stress, sleeping disorders, anxiety, seasonal affective disorder or major depression, cardiovascular pathology, digestive system pathology, insomnia and fatigue due to jet lag, schizophrenia, panic attacks, depression, appetite disorders, obesity, insomnia, mental disorders, epilepsy, diabetes mellitus, Parkinson's disease, senile dementia, various disorders caused by normal or pathological aging, migraine, memory loss, and Alzheimer's disease, is useful against cerebral circulation disorders, is useful for the treatment of hypogonadism, has anovulation and immunomodulatory characteristics, and is useful in the application for the treatment of cancer (Patent Document 2).

(In the formula, R1 represents a C1-6 alkyl group or the like, R2 and R3 are combined with a nitrogen atom to which they are bonded to form 5- to 8-membered heterocycle, in which the heterocycle does not contain an additional hetero atom, and n represents an integer of 2 to 6.)
It has been described that some compounds including compounds represented by the following formulae (C) and (D) have an affinity for MT1 and MT2 receptors (Non-Patent Document 3).

It has been described that some compounds including compounds represented by the following formulae (E) and (F) have an affinity for MT1 and MT2 receptors (Non-Patent Document 4).

It has been described that a compound represented by the formula (G) has an affinity for MT1 and MT2 receptors, is useful for the treatment of stress, sleeping disorders, anxiety, seasonal affective disorder or major depression, cardiovascular pathology, digestive system pathology, insomnia and fatigue due to jet lag, schizophrenia, panic attacks, depression, appetite disorders, obesity, insomnia, pain, mental disorders, epilepsy, diabetes mellitus, Parkinson's disease, senile dementia, various disorders caused by normal or pathological aging, migraine, memory loss, and Alzheimer's disease, is useful against cerebral circulation disorders, is useful for the treatment of hypogonadism, has anovulation and immunomodulatory characteristics, and can be used for the treatment of cancer (Patent Document 3).

(In the formula, G1 represents —X′—(CH2)n—X—(CH2)m—X″—, X represents CH2 or the like, X′ and X″ each represent an oxygen atom or the like, n and m each represent the same or different integers of 0 to 5, Cy represents indole or the like, the indole has a substituent such as a hydrogen atom and a lower alkyl at the 2-position and is bonded to G2 from the 3-position, G2 represents a chain containing 1 to 6 carbon atoms which may be substituted with at least one group such as halogen, A represents NRCOR′ or the like, and R and R′ each represent a hydrogen atom, a C1-6 alkyl group, or the like. Refer to this publication for the other symbols.)
Furthermore, a compound represented by the following formula (H), which has a peripheral MT1 and/or MT2 receptor agonistic activity and is useful against urological diseases, in particular, stress urinary incontinence, has been reported (Patent Document 4).

(In the formula, Y is N or CR1, R1, R3, and R4 are the same as or different from each other and are lower alkyl which may be substituted, H, or halogen, R2 is lower alkyl which may be substituted with at least one substituent selected from a group consisting of halogen and cyano, and further, R2 may be combined with R1 to form —(CH2)n— or R2 may be combined with R3 to form —(CH2)n—, n is 2 or 3, X is a bond, —NR11—, or —NR11—O—, and R6 represents lower alkyl which may be substituted, cycloalkyl which may be substituted, or the like. Refer to this publication for the other symbols.)
In addition, it has been described that melatonin, ramelteon, agomelatine, tasimelteon, and TIK-301, which are compounds having a melatonin receptor activating action, contract the isolated urethra in a rat to increase the urethral pressure of the rat (Patent Document 5).